Opposed view and dual head detector apparatus for diagnosis and biopsy with image processing method

ABSTRACT

The invention relates generally to biopsy needle guidance which employs an x-ray/gamma image spatial co-registration methodology. A gamma camera is configured to mount on a biopsy needle gun platform to obtain a gamma image. More particular, the spatially co-registered x-ray and physiological images may be employed for needle guidance during biopsy. Moreover, functional images may be obtained from a gamma camera at various angles relative to a target site. Further, the invention also generally relates to a breast lesion localization method using opposed gamma camera images or dual opposed images. This dual head methodology may be used to compare the lesion signal in two opposed detector images and to calculate the Z coordinate (distance from one or both of the detectors) of the lesion.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation of copending U.S. Non-Provisional patentapplication Ser. No. 12/688,509, filed Jan. 15, 2010 which is acontinuation of U.S. patent application Ser. No. 11/538,682 filed Oct.4, 2006, now granted as U.S. Pat. No. 7,711,409 on May 4, 2010, entitledOPPOSED VIEW AND DUAL HEAD DETECTOR APPARATUS FOR DIAGNOSIS AND BIOPSYWITH IMAGE PROCESSING METHODS, the disclosures of which are incorporatedby reference herein in their entirety.

BACKGROUND

1. Field of the Invention

The invention relates generally to biopsy needle guidance by employingan x-ray/gamma image spatial co-registration methodology. Further, theinvention relates to using a plurality of gamma camera images taken atdifferent positions to identify breast lesion location. Moreover, theinvention also generally relates to a breast lesion localization methodusing opposed gamma camera images or dual opposed images.

2. Related Art

X-ray imaging of the breast provides high spatial resolution images ofchanges in breast tissue density. These density changes may be due to anumber of factors such as age, pre- and post-menopausal tissue changesand the presence of various pathological conditions. X-ray imaging is acommonly used technique for breast cancer screening and diagnosis, butsince it also is sensitive to other non-malignant pathologies, itsaccuracy is compromised. The specificity of x-ray imaging may be quitepoor with only about 20% to about 35% of biopsies yielding cancerdiagnoses. It is also a commonly used modality for breast tumor needlebiopsy guidance, but has been found to be lacking in target accuracy forsome cases.

Nuclear medicine breast imaging techniques may yield accuratephysiological data, but with a lower spatial resolution than thatobtained with x-ray imaging. This physiological imaging is much morespecific than x-ray imaging, with about 70% of positive studies yieldinga cancer diagnosis. Also, since it detects physiological abnormalities,it directly indicates the location of disease, while x-ray imaging islimited to detecting changes in tissue density which may be secondary tothe presence of disease.

Another important area of diagnostic concern is the accuracy of astereotactic needle biopsy. This biopsy procedure has been proven to beeffective in managing most patients demonstrating suspiciousmammographic findings in screening mammograms. Due to its less invasivenature, this procedure may be more desirable to perform than otherbiopsy procedures. Despite the promising role of this procedure inbreast lesion management, however, some clinical studies have found afalse negative rate of about 10%. Moreover, findings from additionalstudies point toward specific subgroups limiting the diagnostic accuracyof this procedure. The first of these subgroups consists of cases inwhich the needle biopsy underestimated the extent or type of disease. Inthese studies, needle biopsies indicating atypical ductal hyperplasia orductal carcinoma in-situ were often upgraded to infiltrating ductalcarcinoma upon open biopsy or follow-up. In addition, another studyfound that the diagnostic accuracy of needle biopsy was dependent onlesion size, as masses larger than about 3 cm were less likely to bediagnosed correctly.

Scintimammography is a functional, biomolecular breast imaging procedurethat is typically conducted with large field-of-view gamma cameras. Theefficacy of this procedure is lacking for diagnostic accuracy forlesions less than about 1 cm in diameter, non-palpable masses, andlesions located in the medial aspect of the breast. Severalinvestigators have hypothesized that these limitations may be due to theuse of non-optimized large field-of-view detectors and suggested thestudy accuracy could be improved with dedicated small field-of-viewsystems. Such systems may allow the breast to be compressed against thecollimator to optimize image spatial resolution. In addition, thesedetectors may be positioned to allow the breast to be imaged fromseveral angles including the medial views. Improved spatial resolutionmay lead to improved lesion visibility and therefore higher sensitivity.Accordingly, there is a need to improve the exiting imagingmethodologies and techniques.

SUMMARY OF THE INVENTION

The invention satisfies the above needs and avoids the disadvantages anddrawbacks of the prior art by spatially co-registering and fusing gammaimages and x-ray images together to create a single image. This takesadvantage of both the high spatial resolution of the x-ray image and thehigh specificity of the nuclear medicine data. This fused image alsoallows tumor localization with either or both modalities.

According to a principle of the invention, a gamma camera may beremovably attached to a biopsy needle gun platform, thereby permittingcontrol of the acquisition of one or more functional images. The biopsyneedle gun may be reattached and one or more biopsies are performedbased on a co-registered imaged resulting from fusing an x-ray image anda functional image.

According to another principle of the invention, multiple functionalimages using a gamma camera at multiple positions may be obtained. Thefunctional images are then registered together to create a spatiallyco-registered image for tumor and lesion localization and biopsy needlegives guidance and control.

According to a further principle of the invention, functional images atopposing angles may be obtained. The functional images are thenevaluated to determine a three-dimensional location of a tumor.

The invention may be implemented in a number of ways. According to oneaspect of the invention, a method for lesion localization in a targetsite of a patient is provided. According to this aspect a first imagefrom an imaging device located at a first image position is obtained; asecond image from an imaging device located at a second image positionis then obtained and an X coordinate of the lesion within the targetsite of the patient based upon the first image and the second image iscalculated, a Y coordinate of the lesion within the target site of thepatient based upon the first image and the second image is calculated,and a Z coordinate of the lesion within the target site of the patientbased upon the first image and the second image is calculated. In afurther aspect, radiotracer uptake may be calculated based upon the X,Y, and Z coordinates. Calculating the Z coordinate of the lesion mayinclude comparing the comparative signal intensity and the spatialresolution data in the first image and the second image.

In an additional aspect, the first image may be generated by a firstx-ray detector and the second image may be generated by a second x-raydetector positioned about 180° relative to the first x-ray detector.Alternatively, the second image may be generated by a gamma camerapositioned about 180° relative to the first x-ray detector. Furthermore,the second image may be generated by a gamma camera positioned about180° relative to the first gamma camera.

In another aspect of the invention, the target site may be the breast,thyroid, parathyroid, heart, liver, kidney, gall bladder, bladder,reproductive organs and glandular structures.

Another aspect of the invention provides an apparatus for determininglesion location within a target site in a patient. The apparatus mayinclude at least one gantry; and at least one imaging device mounted onthe at least one gantry, where the at least one imaging device may bemovable with respect to the target area of the patient such that the atleast one imaging device acquires a plurality of images at a pluralityof positions relative to the target site in the patient. Furthermore,the apparatus may include a controller configured to control movement ofthe at least one imaging device, to be capable to receive images fromthe at least one imaging device, and to be capable to calculate thelesion location within the target site of the patient based upon theplurality of images generated from said at least one imaging device.Additionally, the apparatus may include a pair of compression paddles.

In a further aspect, the first imaging device may be an x-ray generatormounted on a first gantry and the second imaging device may be an x-raydetector mounted on the first gantry and the third imaging device may bea gamma camera mounted on a second gantry. In yet a further aspect, theapparatus may also include a fourth imaging device which is a gammacamera mounted on the second gantry.

An additional aspect provides that the first gantry and the secondgantry may be concentric moveable rings with respect to each other.Furthermore, the first imagining device may be a gamma camera mounted onthe first gantry, the second imaging device may be an x-ray generatormounted on the second gantry and the third imaging device may be anx-ray detector mounted on the second gantry. In an additional aspect,the fourth imaging device may be a gamma camera mounted on the firstgantry. The first and second gantry may be concentric rings which aremoveable with respect to each other.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are included to provide a furtherunderstanding of the invention, are incorporated in and constitute apart of this specification, illustrate embodiments of the invention andtogether with the detailed description serve to explain the principlesof the invention. No attempt is made to show structural details of theinvention in more detail than may be necessary for a fundamentalunderstanding of the invention and various ways in which it may bepracticed. In the drawings:

FIG. 1 is a schematic illustration of the detector system illustrating agamma camera mounted to an existing x-ray stereotactic biopsy tableconstructed according to principles of the invention;

FIG. 2 illustrates resulting x-ray images, gamma camera images andco-registered images from a patient study implemented according toprinciples of the invention;

FIG. 3 provides a schematic illustration of a gamma camera mounted on agantry allowing the gamma camera to move among a plurality of positionsrelative to the breast constructed according to principles of theinvention;

FIG. 4 is a flow chart illustrating a method for determining whether alesion is a true-positive or a false-positive according to principles ofthe invention;

FIG. 5 is a schematic illustration of an opposed dual head detectorapparatus constructed according to principles of the invention;

FIG. 6A provides a schematic illustration of a top view of a moveablemounting gantry for use in the system constructed according toprinciples of the invention;

FIG. 6B provides a schematic illustration of a cut-away view of themounting gantry of FIG. 6A;

FIG. 7 is a graph illustrating the lesion contrast as a function ofdepth in a phantom for a 1 cm diameter spherical lesion phantom in a 10cm thick breast phantom with a 6:1 lesion-to-background ration;

FIG. 8 is a graph illustrating system resolution with increasing sourceto detector distance for both high resolution and high efficiencycollimators;

FIG. 9A shows phantom images from the single gamma camera system in anexample using principles of the invention;

FIG. 9B show the lineout graphs demonstrating the lesion contrast ineach of the detector images and in each of the image fusion techniquesof the example in FIG. 9A;

FIG. 10A shows 10 minute static acquisitions from different detectorhead positions and the contrast map images in an example usingprinciples of the invention;

FIG. 10B shows the lineout graphs demonstrating the lesion contrast foreach of the three images of the example of FIG. 10A;

FIG. 11A shows unsmoothed and smoothed images from the PEM system usinga phantom filled with F-18 (6:1 lesion-to-phantom concentration ratio)in an example using principles of the invention;

FIG. 11B shows the vertical lineout graph through the lesion from theunsmoothed PEM image of the example of FIG. 11A;

FIG. 12A shows the SPECT reconstruction of the cylinder phantom in anexample using principles of the invention; and

FIG. 12B provides the lineout graphs for each of the 8 mm lesions seenin slices 2 and 7 respectively of the example of FIG. 12A.

FIG. 13 shows an X-ray (Panel I), a gamma image (Panel II), and acoregistered and overlaid X-ray and gamma image (Panel III). Panel IVshows a standard camera image indicating a false negative study for thispatient.

FIG. 14 shows radiotracer uptake in the gamma image (Panel I),suspicious microcalcifications in the X-ray image (Panel II), and anoverly image demonstrating a poor spatial correlation of the images(Panel III).

FIG. 15 shows an uptake curve where the lesion uptake is very high andthis case was determined via needle biopsy to be an infiltrating ductalcarcinoma with high nuclear grade.

FIG. 16 is a graph showing data points for several of the true positivecases and for all of the false positive cases. Linear fits for each dataset were applied (true positive fits in solid lines and false positivefits in dotted lines). Note the positive slope of the true positivecases and the negative slope of the false positive cases.

DETAILED DESCRIPTION OF THE INVENTION

It is understood that the invention is not limited to the particularmethodology, protocols, and reagents, etc., described herein, as thesemay vary as the skilled artisan will recognize. It is also to beunderstood that the terminology used herein is used for the purpose ofdescribing particular embodiments only, and is not intended to limit thescope of the invention. It also is noted that as used herein and in theappended claims, the singular forms “a,” “an,” and “the” include theplural reference unless the context clearly dictates otherwise. Thus,for example, a reference to “a lesion” is a reference to one or morelesions and equivalents thereof known to those skilled in the art.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meanings as commonly understood by one of ordinary skillin the art to which the invention pertains. The embodiments of theinvention and the various features and advantageous details thereof areexplained more fully with reference to the non-limiting embodiments andexamples that are described and/or illustrated in the accompanyingdrawings and detailed in the following description. It should be notedthat the features illustrated in the drawings are not necessarily drawnto scale, and features of one embodiment may be employed with otherembodiments as the skilled artisan would recognize, even if notexplicitly stated herein. Descriptions of well-known components andprocessing techniques may be omitted so as to not unnecessarily obscurethe embodiments of the invention. The examples used herein are intendedmerely to facilitate an understanding of ways in which the invention maybe practiced and to further enable those of skill in the art to practicethe embodiments of the invention. Accordingly, the examples andembodiments herein should not be construed as limiting the scope of theinvention, which is defined solely by the appended claims and applicablelaw. Moreover, it is noted that like reference numerals referencesimilar parts throughout the several views of the drawings.

Moreover, provided immediately below is a “Definition” section, wherecertain terms related to the invention are defined specifically.Particular methods, devices, and materials are described, although anymethods and materials similar or equivalent to those described hereincan be used in the practice or testing of the invention. All referencesreferred to herein are incorporated by reference herein in theirentirety.

DEFINITIONS

PSPMT is position sensitive photomultiplier tubes.

FDG (F-18) or F-18 is fluoro-2-deoxyglucose.

PEM is positron emission mammography.

SPECT is single photon emission computed tomography.

ROI is region of interest.

BKG is baseline tissue uptake curve.

AOC is area of concern.

PPV is positive predictive value.

NPV is negative predictive value.

The term “radiopharmaceutical” generally refers to tracers used in thediagnosis and treatment of many diseases, including without limitation,breast cancer, and for imaging and function studies of the brain,myocardium, thyroid, lungs, liver, gallbladder, kidneys, skeleton, bloodand tumors. Radiopharmaceuticals suitable for use with the invention mayinclude but are not limited to, technetium (Tc-99m), FDG, sestaMIBI(Tc-94m), Tl-201 chloride, or any other imaging specific reagent.

The term “functional image” or “physiological data” generally refers toan image generated from detection of a radiopharmaceutical.

The term “non-functional image” or “anatomical data” generally refers tothe image(s) generated by an x-ray detector.

“Patient” as used herein, refers to an individual who requires detectionand diagnosis of possible disease, such as breast cancer. Furthermore,the term “subject” includes animals and humans.

“Target tissue,” as used herein generally refers to any tissue in thebody of any animal, including the human body that composes all theorgans, structures and other contents. Specifically, a tissue is anysubstance made up of cells that perform a similar function with anorganism. For example, tissue may refer to any epithelial tissue, breasttissue, connective tissue, muscle tissue, such as cardiac, smoothmuscle, and skeletal, and any nervous tissue, such as tissue within thebrain, spinal cord, and/or peripheral nervous system.

One aspect of the invention generally relates to a mounting mechanism toadapt a gamma camera (also referred to herein as a “detector head” or a“head”) to a stereotactic needle core biopsy machine. Thus, a system isprovided that employs the mechanical mount of the needle driver platformof a commercial stereotactic biopsy table to attach a smallfield-of-view gamma camera. This platform permits various needle guns tobe utilized. Since the accuracy of biopsy is dependent on the mechanicalalignment of this gun to the x-ray images, it is an excellent mountingsurface for other devices requiring such alignment. By employing thismount as a stage for the gamma camera, the image taken by the gammacamera may be aligned with the image taken by the x-ray without the useof additional alignment tools. This method may allow image fusion andlesion localization by combining data generated from a gamma camera anddigital x-ray detector. Further, this method uses spatiallyco-registered x-ray and physiological images for needle guidance duringbiopsy. Following imaging, the gamma camera may be removed from themounting platform and replaced with the needle gun to implement thebiopsy procedure. The biopsy may be performed based on the spatiallyco-registered image.

Additionally, the invention generally relates to a multiple anglestereotactic gamma guided biopsy system. This multiple angle system maybe used to image the breast from multiple angles. Use of multiple headsmay allow simultaneous imaging thereby reducing the stereotacticimagining time compared to a single head system. Also, the multipleangle system, when implemented using multiple heads, may allow dynamicradiotracer wash-in studies to be simultaneously viewed from multipleangles.

Moreover, another aspect of the invention generally relates to a breastlesion localization method using opposed gamma camera images or dualopposed images. This dual head methodology may be used to compare thelesion signal in two opposed detector head images and to calculate the Zcoordinate (distance from one or both of the detectors) of the lesion.Other types of images may also be used. Moreover, the inventiongenerally relates to a method for breast lesion uptake quantificationusing a dual head detector. This quantification method may be used toderive the radiotracer concentration within a specific volume of tissuefrom an opposed dual position gamma camera acquisition. Additionally,the dual head system may be used for image fusion and processing forincreased lesion detectability, 3-dimensional localization, lesionradiotracer concentration and biopsy guidance.

According to an embodiment of the invention, a small field-of-view gammacamera is attached to the mechanical mount of the needle driver platformof a commercial stereotactic biopsy table, such as any conventionalLorad or Fischer-type stereotactic tables. The mechanical accuracy ofthis mount and its alignment with the x-ray detector allows the x-rayand gamma camera images to be co-registered reliably, and facilitatesdirect image fusion without the use of software alignment. Gamma camerasfor use in the system of the invention have been described in U.S. Pat.No. 6,389,098, which is expressly incorporated herein by reference inits entirety. Since the detectors are mechanically aligned, this fusionprocess is straight forward and may allow the physician to evaluate boththe anatomical data (x-ray) and the physiological data (gamma) in asingle image to better determine the location of a lesion and thereforeimprove and/or optimize needle localization. It may also allow thelocalization to be calculated with the existing cursor system in thex-ray system if the gamma camera image is imported and fused to thex-ray image in the system software.

FIG. 1 is a schematic diagram of the detector system illustrating agamma camera mounted to an existing x-ray stereotactic biopsy tableaccording to principles of the invention. A system 100 for a core biopsydevice is provided. In this embodiment, the system 100 includes a table102, a hole or aperture 104, compression paddles 106, an x-ray generator108, an x-ray detector 110, a support arm 112, a gamma camera 114, suchas a scintimammography, gamma sensitive mini-camera, on a removablepositioning stage 120, and a controller 122.

Referring back to FIG. 1, the table 102 may include an aperture or hole104 for pendantly accepting the breast of a patient (not shown) lyingface down on table 102. Below aperture 104 are conventional compressionpaddles 106 that receive and compress the breast under examination.Compression paddles can be solid or fenestrated for biopsy access. Also,the compression paddles can move in and out. An x-ray generator 108 anda x-ray detector 110, such a digital x-ray detector, are mounted atopposing ends of a platform 116 that is allowed to rotate about axis ofrotation 118. A gamma camera 114 is located proximate compressionpaddles 106 and arranged to obtain one or more images that can beregistered with those obtained by the x-ray generator 108 and the x-raydetector 110. The gamma camera may be removeably mounted on apositioning platform 120 that rotates about its axis of rotation 118such that the gamma camera can be rotated out of any obstructingposition during acquisition of the x-ray images and then rotated intoposition to obtain one or more images before or after acquisition of thex-ray images.

In using a system of the invention, the patient undergoing examinationis first injected with a suitable radiopharmaceutical. Here, the systemof the invention utilizes the higher uptake of certainradiopharmaceuticals by the organ or tissue of interest, therebyallowing the selected organ/tissue to be imaged. For example, malignanttissues preferentially absorb the radiopharmaceutical, such as Tc-99m,SestaMIBI, and Tl-201 chloride, in direct comparison to benign masses(except for some highly cellular adenomas). Therefore, theseradiopharmaceuticals can be used to help diagnose and differentiatetumors from benign growths, for example in the system of the inventionfor breast cancer detection and diagnosis. Possible mechanisms foruptake of Tl-201 chloride into tumor cells include the action of theATPase sodium-potassium transport system in the cell membrane whichcreates an intracellular concentration of potassium greater than theconcentration in the extracellular space. Thallium may be significantlyinfluenced by this transport system in tumors. In addition, aco-transport system has been identified which also is felt to beimportant in uptake of thallium by tumor cells.

Following injection of the radiopharmaceutical, the patient is placed onthe above-described examination table 102 with one breast extendingthrough aperture 104. The paddles 106 are compressed about the breast inthe conventional fashion, and one or more X-ray images are acquired inthe conventional manner while gamma camera 114 is moved out of the fieldof view of X-ray detector 110. Gamma camera 114 is then moved intoposition and one or more images are acquired with gamma camera 114.

A further embodiment of the invention generally relates to a method forimage fusion and lesion localization by combining data from a gammacamera and an x-ray detector. A computer software program to spatiallyco-register the images obtained by each of these modalities and fuse thedata to form a single image containing physiological and anatomicalinformation is employed. Representative computer software programs mayinclude IDL (RSI, Boulder, Co), Nuc-med image, and O-sires. Once theX-ray image(s) are registered electronically with the gamma image(s),any lesions and their location may be positively located.

FIG. 2 illustrates resulting x-ray images, gamma camera images andco-registered images from a patient study described in specific example3, infra, implemented according to principles of the invention.According to an embodiment of the invention, both the x-ray images andthe gamma images are digital, as is the resulting co-registered image.Because of the higher malignancy determination capability of the gammacamera, better decisions can be made as to whether a biopsy by anyconventional method is required and what biopsy method should be used. Amethod according to principles of the invention may use the spatiallyco-registered x-ray and gamma (nuclear medicine) images for needleguidance during a biopsy.

In an additional embodiment, after imaging, the gamma camera may beremoved from the positioning platform and replaced with any conventionalbiopsy needle gun. The needle gun may be mechanically aligned based onthe co-registered x-ray and gamma images, thereby allowing a moreaccurate biopsy to be performed.

The breast biopsy involves inserting a needle into a suspicious lesionin a breast to obtain a tissue sample. With reference to FIG. 1, thebiopsy needle may be attached to an automated high-speed injection gun,which may be mounted on the positioning platform 120 that accommodatedthe gamma camera 114 and which now may be used to guide the placement ofthe biopsy needle. Once the x-ray and gamma images have beenco-registered, a controller 122 then uses the co-registered images tocalculate the specific position of the suspicious lesion. Once thespecific position of the lesion has been determined, the needle isinserted into the breast and the injection gun is fired one or moretimes to remove samples from different portions of the lesion. Thesamples are sent to a pathologist for evaluation.

According to an embodiment of the invention, the concentration ofradiotracer within the lesion of the target tissue may be determined,which may be useful in differentiation of true-positive lesions fromfalse-positive lesions within the target tissue. This may beaccomplished by acquiring multiple functional images at various anglesrelative to a vertical axis of the target site to be evaluated, such asa breast. For example, the gamma camera mounting gantry may allow thegamma camera to be positioned in at least three positions relative tothe breast, such as at about 0°, about +15°, and about −15°.

FIG. 3 provides a schematic illustration of a gamma camera mounted on agantry allowing the gamma camera to move among a plurality of positionsrelative to the breast according to principles of the invention.Referring to FIG. 3, a table 302 with an aperature 304 is shown. Breast324 is immobolized between two compression paddles (not shown) relativeto gamma camera 314, which is mounted in track 322. Gamma camera 314 ispositioned at about 0° relative to the breast 324 and is capable ofmoving along tack 322 to various angles relative to the breast. Forexample, gamma camera 324 may be positioned about +15° relative to thebreast or about −15° relative to the breast. Alternatively, the cameramay be positioned at other angles besides about ±15°, such as angles inthe range of about −45° to about ±45°.

The target tissue to be evaluated should not be construed to be limitedsolely to the breast, as other targets, e.g., colon, prostate, breast,thyroid, parathyroid, heart, liver, kidney, gall bladder, bladder,reproductive organs and glandular structure may be targeted for imaging.Additionally, the positions of the gamma camera should not be construedto be limited to the specific angles values related herein, butadjustments of the angle of the positions, including the number of viewsthat may be used to calculate the radiotracer concentration within thelesion, may be made as determined by the radiologist.

FIG. 4 is a flowchart illustrating a method for determining whether alesion is a true-positive lesion or a false-positive lesion according toprinciples of the invention. In step 402, a physician determines thetarget site to be evaluated. In step 404, the appropriateradiopharmaceutical is selected based upon patient, target site andphysiological process to be evaluated. In step 406, theradiopharmaceutical is administered to the patient. Subsequently, one ormore functional and/or anatomical images are obtained in step 408. Analgorithm is employed in step 410 and calculates the radiotracerconcentration in the lesion in step 412. Finally, a physician willevaluate whether the lesion in the target site is a true-positive lesionor a false-positive lesion. The flowchart of FIG. 4 will now bedescribed in greater detail below.

The target site to be evaluated in the patient is determined at step402. Subsequently, a physician determines the appropriateradiopharmaceutical to use based upon the patient, the target site,and/or the physiological process desired to be evaluated at step 404.The radiopharmaceutical is introduced into the body at step 406.

The radiopharmaceutical is often bound to a compound that actscharacteristically within the body and is commonly known as a tracer. Inthe presence of disease, a tracer will often be distributed around thebody and/or processed differently. For example, the ligandmethylene-diphosphonate (MDP) can be prefentially taken up by bone. Bychemically attaching technetium-99m to MDP, radioactivity can betransported and attached to bone for imaging. Any increasedphysiological function, such as due to a fracture in the bone, mayresult in the appearance of a hot spot which is a focal increaseradio-accumulation, or a general increase in radio-accumulationthroughout the physiological system. Alternatively, some diseaseprocesses may result in the exclusion of a tracer, thereby resulting inthe appearance of a cold-spot. Many different tracer complexes have beendeveloped in order to image many different organs, glands, andphysiological processes. Thus, one skilled in the art would understandthe appropriate radiopharmaceutical to administered to the patient basedupon the target site and/or the physiological process. Moreover, asdescribed above, other radiopharmaceuticals may be used for identifyinglesions in the breast. The radiopharmaceuticals may include, forexample, Technetium-99m, iodine-123, iodine 131, thallium-201,gallium-67, fluroine-18, xenon-133, krypton-81m, and Technegas®.

The radiopharmaceutical may be administered by intravenous injection,subcutaneous injection, intrasynovial injection, inhalation, injestion,intrathecal injection, and topical application. For intravenousinjection, the radiopharmaceutical is injected in the vein. Manydifferent types of evaluations may be accomplished using this method,such as the technetium-99m-MDP bone scan. With subcutaneous injection,the radiopharmaceutical is injected under the skin, and may be used wheninvestigating the lymphatic system. Moreover, intrasynovial injectionmay be used when examining a joint space, such as knee joint. In thismethod, a radiopharmaceutical, such as yttrium-90, is injected directlyinto the joint space. Some radiopharmaceuticals may be inhaled by thepatient, typically when investigaing the lungs. For example, gases suchas kyrpton-81m, and aerosols, including technetium-99m, may beadministered to the pateint. Additionally, the radiopharmaceutical maybe administered to the patient by intrathecal injection. With thismethod, the radiopharmaceutical in injected into the subarachnoid space,usually via lumbar punture and is generally used when investigating thecerebrospinal fluid (CSF) circulation or for detecting CSF leaks. Theradiopharmaceutical also may be administered topically to the patient.Using this method, the radiopharmaceutical is directly delivered to thearea to be investigated, such as the administration of technetium-99meyedrops to investigate the tear-duct flow.

Following administration of the appropriate radiopharmaceutical to thepatient, the radiation emitted by the patient may be detected at step408, using an imager, such as a gamma camera, such that one or morefunctional images may be obtained. One or more x-ray images may also beobtained. According to an embodiment of the invention, the gamma cameramounting gantry may allow the gamma camera to be positioned in multiplepositions relative to the target site to be evaluated. By way ofexample, three positions may be located on a stereotactic arc of about0°, about +15, and about −15°. FIG. 3 described above, for example,provides a schematic illustration of a system 300 having at least onegamma 314 camera capable of positioning in a plurality of positionsrelative to the breast 324. As illustrated in FIG. 3, the system 300includes a table 302 having an aperture 304. A patient's breast 324 isplaced within the aperture 324. In this placement, one or more camerasmay be used at varying positions along the track 322 relative to thebreast 324. This arch may allow the stereotactic localization to becompleted with the gamma images alone.

Once the gamma images have been obtained, an algorithm may be applied tothe gamma image data at step 410. For example, by using a backprojection technique from each of the three views, a gross estimation oflesion volume may be made using this data along with the breastcompression thickness, resolution and attenuation corrections, anddetector quantum efficiency.

At step 412, the absolute concentration of radiotracer in the lesion iscalculated after obtaining at least three projections (e.g., at −15°,0°, and +15°) of the lesion. This dataset allows the z-coordinate to becalculated and for the lesion dimensions of height, width, and length tobe measured in the three projections. From these measurements, a roughlesion volume is calculated. Next, using the 0° image, a ROI for thelesion is drawn and the total counts in the region is measured fordetector sensitivity, impact of detector resolution, and attenuation,the absolute activity for the region is calculated (mCi). After thebackground noise is subtracted, the remaining value is corrected volumeresulting in mCi/ml or some other activity per volume value. This valuemay be useful in differentiating true-positive from false-positive casesat step 414. While a method according to principles of the invention hasbeen described in FIG. 4, it is understood that additional steps may beadded to the method, steps may be omitted from the method and/or stepsmay be performed in a different order without departing from the scopeof the invention.

Moreover, by incorporating dynamic radiotracer uptake quantification,radiotracer wash-in may be analyzed for differentiation. Both of thesemethods may allow more detailed studies of radiotracer pharmacokineticsthan previous systems. Although stereotactic biopsy may be possible withthese three views alone, the gamma detector may be mounted on the archusing a motorized system allowing images to be obtained anywhere alongthe arch. This precision motor controlled movement would make the systemcapable of limited angle tomographic imaging. If the x-ray system isenabled to do tomographic imaging as well, this would allow fusionbetween the tomographic modalities.

According to an embodiment of the invention, a system employs only onegamma detector head. Since three views are required for localization andeach of these views requires several minutes, alternative embodimentsmay employ multiple heads to reduce study time while allowing theradiotracer wash in to be recorded from multiple angles. According to anembodiment of the invention, if a system employs two gamma detectorheads, one could be fixed at an about +15° view while the other couldrotate between an about −15° view and an about 0° view. A triple gammadetector head system would allow detectors to be mounted in all threestereotactic positions simultaneously for an even greater study timereduction. Other configurations may also be used.

Therefore, according to embodiment of the invention, a two or threedetector head nuclear medicine imaging system may be employed to provideimages simultaneously from multiple angles, thereby reducing thestereotactic imaging time compared to a single detector head system. Inaddition, the system may allow dynamic radiotracer wash-in studies to besimultaneously viewed from multiple angles.

According to an embodiment of the invention, two opposed gamma cameraimages of radiopharmaceutical uptake within a target site, such as thebreast, may be utilized to determine the X, Y, and Z coordinates of alesion for the purpose of biopsy. For example, a detector or detectorsare positioned on either side of an immobilized breast. FIG. 5 is aschematic illustration of an opposed dual head detector apparatusaccording to principles of the invention. The apparatus includes abreast 502 immobilized between compression paddle 504 and compressionpaddle 506. Imaging device 508, imaging device 512, imaging device 510,and imaging device 514 are positioned to obtain images of breast 502. Byway of example, imaging device 508 may be an x-ray generator, imagingdevice 512 may be an x-ray detector, imaging device 510 may be a gammacamera and imaging device 514 may be a gamma camera.

The imaging system described in the embodiment of FIG. 5 should not beconstrued to be limited to this configuration, but may be configured inany number of ways. For example, the system may only include imagingdevice 508, which may be an x-ray generator, and imaging device 506,which may be an x-ray detector. Alternatively, imaging device 508 may bea gamma camera and imaging device 510 may be an x-ray generator andimaging device 514 may be an x-ray detector.

Lesion location may be determined in one or both acquired images. The Zlocation may be calculated by comparing the signal of lesion in theacquired images, such as by using comparative signal intensity andspatial resolution. For example, this may be done by comparingfunctional images from one or more gamma cameras. Since it can beassumed that the detector heads are looking at the same foci, a lesionlocated equidistant from both detector heads would yield very similarsignal characteristics. If the lesion is closer to one detector headthan to the other, attenuation and resolution changes result in a changein signal for both detector heads. By measuring and modeling thesechanges, the Z location of the lesion may be determined. Although thislesion localization methodology has been described above using gammacameras, it is understood that other types of imaging may be used.

Using the lesion X, Y and Z location from the method discussed above,the sensitivity of the detector, the breast compression thickness and asimple attenuation model, the specific activity for the lesion volumecan be determined. According to an embodiment of the invention, a methodfor determining specific activity may begin with determining the height(Y coordinate) and width (X coordinate) of the mass using the acquiredimages. The thickness (Z coordinate), is assumed to be the mean of theheight and width. Based on these parameters, the volume of the lesion iscalculated. A region of interest (ROI) is drawn around the lesion andthe number of counts in the region is determined. The same sized ROI isdrawn in the background and number of counts is determined. The numberof counts in the background is divided by the area of the ROI in mm andthen by the breast thickness in mm, where the resulting value isexpressed as (counts per mm³). The lesion height is subtracted from thetotal breast thickness, and the result is the height of backgroundtissue above and below the lesion in the lesion ROI. The backgroundtissue height is multiplied by the value of the background countsdivided by the area ROI. The result is the number of non-lesioncounts/mm³ in the lesion ROI. The number of non-lesion counts issubtracted from the counts/mm³ in the lesion ROI, where the result isthe number of counts from the area of the lesion. The number of countsfrom the area of the lesion is divided by the height of the lesion. Thisresult is the counts per volume. The counts per volume are multiplied bya correction factor accounting for the efficiency of the detectorsystem. This final result is the concentration value. This concentrationvalue (mCi/mm³) is a better measure of lesion uptake than contrast (thecurrent method for evaluation) which is dependent on lesion volume.Other methods may also be used.

The gantry mount embodiment described previously may include a gantrywith a breast immobilization device and one or more gamma cameras forimaging. The gamma camera or cameras are capable of acquiring opposedviews of the immobilized breast. The gamma camera or cameras may bemounted such that they may be moved into an imaging position around thebreast or swung out of the way to allow access to the breast for biopsy.The immobilization device may be designed to allow a biopsy to beconducted through the walls of the device or through provided accesspanels.

Alternatively, the gamma camera may be mounted on a gantry havingconcentric sliding rings. FIG. 6A provides a schematic illustration of atop view of a moveable mounting gantry according to principles of theinvention. FIG. 6B provides a schematic illustration of cut-away viewsof the mounting gantry of FIG. 6B. A system 600 includes a stationarymount 602, an inner concentric sliding ring 604, and an outer concentricsliding ring 606. Compression paddles 608 are moveably mounted onstationary mount 602. An x-ray generator 610 is mounted on the innerconcentric ring 604, and an x-ray detector 612 is mounted on the innersliding ring 604. A gamma camera 614 is mounted on the outer concentricsliding ring 606 and a gamma camera 616 is mounted on the outerconcentric sliding ring 606. FIGS. 6A and 6B are exemplary and shouldnot be construed to be limit to this particular configuration.

The concentric ring 604 permits the x-ray detector 612 and the x-raygenerator 610 to move relative to the target while still maintaining thealignment between the x-ray generator 610 and the x-ray detector 612.Further, concentric ring 606 permits the gamma cameras 614 and 616 tomove relative to the target while still maintaining the alignmentbetween the gamma cameras 614 and 616.

The gantry system 600 may be capable of accommodating the compressionpaddles 608, gamma cameras 614 and 616, x-ray detectors 612, or x-raygenerators 610. Moreover, if the rings 604, 606 are equipped withcompression paddles 608, the paddles 608 can slide in and out toaccommodate breast size variation as conventional paddles, such as withset screws, stepper motor, etc. (not shown). Alternatively, thecompression paddles 608 may be rigidly fixed to the rings 604, 606 andallow the rings 604, 606 to have an adjustable array of radii. Theconcentric sliding rings 604, 606 may be mounted to a “wheel in place”gantry which would not interfere with mammographic or stereotacticequipment. The gantry may move in front of the patient for imaging andthen be simply wheeled away when the imaging is completed.

Of the available radiotracers, the invention may compatible for usewith, but not limited to imaging abscess and infection by using galliumcitrate Ga 67, and indium In 111 oxyquinoline; biliary tract blockageusing technetium Tc 99m disofenin, technetium Tc 99m lidofenin, andtechnetium Tc 99m mebrofenin; blood volume studies usingradioiodinatedaAlbumin, sodium chromate Cr 51; blood vessel diseasesusing sodium pertechnetate Tc 99m; blood vessel diseases of the brainusing ammonia N 13, iofetamine I 123, technetium Tc 99m bicisate,technetium Tc 99m exametazime, and xenon Xe 133; bone diseases usingsodium fluoride F 18, technetium Tc 99m medronate, technetium Tc 99moxidronate, technetium Tc 99m pyrophosphate, and technetium Tc 99m(pyro- and trimeta-) phosphates; bone marrow diseases using sodiumchromate Cr 51, technetium Tc 99m albumin colloid, and technetium Tc 99msulfur colloid; brain diseases and tumors using fludeoxyglucose F 18,indium In 111 pentetreotide, iofetamine I 123, sodium pertechnetate Tc99m, technetium Tc 99m exametazime, technetium Tc 99m gluceptate, andtechnetium Tc 99m pentetate; cancer and tumors using fludeoxyglucose F18, gallium citrate Ga 67, indium In 111 pentetreotide, indium In 111iatumomab pendetide, methionine C 11, radioiodinated iobenguane, sodiumfluoride F 18, technetium Tc 99m arcitumomab, and technetium Tc 99mnofetumomab merpentan; colorectal disease using technetium Tc 99marcitumomab; disorders of iron metabolism and absorption using ferrouscitrate Fe 59; heart disease using ammonia N 13, fludeoxyglucose F 18,rubidium Rb 82, sodium pertechnetate Tc 99m, technetium Tc 99m albumin,technetium Tc 99m sestamibi, technetium Tc 99m teboroxime, technetium Tc99m tetrofosmin, and thallous chloride Tl 201; heart muscle damage(infarct) using ammonia N 13, fludeoxyglucose F 18, rubidium Rb 82,technetium Tc 99m pyrophosphate, technetium Tc 99m (pyro- and trimeta-)phosphates, technetium Tc 99m sestamibi, technetium Tc 99m teboroxime,technetium Tc 99m tetrofosmin, and thallous chloride Tl 201; impairedflow of cerebrospinal fluid in brain using indium In 111 pentetate;kidney diseases using iodohippurate sodium I 123, iodohippurate sodium I131, iothalamate sodium I 125, technetium Tc 99m gluceptate, technetiumTc 99m mertiatide, technetium Tc 99m pentetate, and technetium Tc 99msuccimer; liver diseases using ammonia N 13, fludeoxyglucose F 18,technetium Tc 99m albumin colloid, technetium Tc 99m disofenin,technetium Tc 99m lidofenin, technetium Tc 99m mebrofenin, andtechnetium Tc 99m sulfur colloid; lung diseases using krypton Kr 81m,technetium Tc 99m albumin aggregated, technetium Tc 99m pentetate, andxenon Xe 127, xenon Xe 133; parathyroid diseases and parathyroid cancerusing technetium Tc 99m sestamibi, thallous chloride Tl 201; perniciousanemia and improper absorption of vitamin B₁₂ from intestines usingcyanocobalamin Co 57; red blood cell diseases using sodium chromate Cr51; salivary gland diseases using sodium pertechnetate Tc 99m; spleendiseases using sodium chromate Cr 51, technetium Tc 99m albumin colloid,and technetium Tc 99m sulfur colloid; stomach and intestinal bleedingusing sodium chromate Cr 51, sodium pertechnetate Tc 99m, technetium Tc99m (gyro- and trimeta-) phosphates, and technetium Tc 99m sulfurcolloid; stomach disorders using technetium Tc 99m sulfur colloid; tearduct blockage using sodium pertechnetate Tc 99m; thyroid diseases andthyroid cancer using fludeoxyglucose F 18, indium In 111 pentetreotide,radioiodinated iobenguane, sodium iodide 1123, sodium iodide 1131,sodium pertechnetate Tc 99m, and technetium Tc 99m sestamibi; andurinary bladder diseases using sodium pertechnetate Tc 99m.

Without further elaboration, it is believed that one skilled in the art,using the preceding description, can utilize the invention to thefullest extent. The following examples are illustrative only, and notlimiting of the disclosure in any way whatsoever.

EXAMPLES

Phantom studies have indicated that two techniques can substantiallyenhance lesion contrast and signal-to-noise ratios. First of all,applying breast compression reduces the cross-sectional thickness ofbreast tissue which improves lesion contrast. Secondly, the minimizationof lesion-to-detector distance dramatically improves lesion signal byreducing signal losses due to attenuation and decreased collimatorresolution. FIG. 7 is a graph illustrating the lesion contrast as afunction of depth in a phantom for a 1 cm diameter spherical lesionphantom in a 10 cm thick breast phantom with a 6:1 lesion-to-backgroundratio. Specifically, the contract reduces as distance increases. Giventhese two observations, a system comprised of two opposed detector headscompressing the breast was provided that yielded improved visualizationof breast lesions. To evaluate this concept, several studies withcompressed breast (e.g., a mean thickness of about 6 cm+/− about 1.5 cm)and lesion phantoms containing an about 6:1 lesion-to-background tracerconcentration ratio were conducted. The results of these experimentsindicated that lesions with a diameter of about 8 mm or greater wereeasily visible in both detectors while lesions of about 5 mm and smallerwere difficult to detect, especially if located near the center of thebreast. For these centrally located lesions, some level of lesion signalwas often present in both detectors, but not truly distinguishable abovenoise. The following specific examples describe a series of experimentsthat were used to evaluate the two image processing techniques ofgeometric mean and contrast mapping. In addition, a comparison betweenthis dual detector approach to single gamma and positron tomographictechniques was conducted in specific examples immediately below.

In the specific examples immediately below, gamma camera prototypes werebased on an array of compact Hamamatsu R7600-00-C8 position sensitivephotomultiplier tubes (PSPMTs). The PSPMT array was optically coupled toa high quality pixellated NaI(Tl) array manufactured by BicronCorporation (Milford, N.H.). The scintillator array was a matrix ofabout 3 mm× about 3 mm× about 6 mm crystals encapsulated in a compacthousing with about a 5 mm thick glass window. Each NaI(Tl) pixel elementwas separated by about 0.3 mm septa made of diffusing white epoxy. Theaverage system energy resolution was about 17.5% FWHM at about 140 keV.

The system was fitted to have a high resolution or a high efficiency,depending on the specific requirements of the experiment, as shown inTable 1 immediately below.

TABLE 1 Hole Diameter Height Septa High Resolution 1.778 19.99 0.305High Efficiency 1.397 27.000 0.203

For example, all SPECT studies were conducted with the high resolutioncollimator to preserve study resolution at greater distances since thecenter-of-rotation to collimator distance was about 10 cm. FIG. 8 is agraph illustrating system resolution with increasing source to detectordistance for both the high resolution and high efficiency collimators.

Specific Example 1

This example utilized an about 5 cm thick plastic breast phantom with anabout 6 mm hollow sphere lesion located near the center of the breastphantom. The breast volume was filled with a Tc99m solution with aconcentration of about 0.33 μCi/ml and the lesion volume concentrationwas about 1.98 μCi/ml. Two opposing 10 minute acquisitions wereobtained. A pair of Co-57 point sources was taped to the edge of thephantom to aid in alignment of the opposing views.

The phantom was then emptied and refilled with F-18 for imaging with adedicated small field-of-view positron breast imaging system, (PEM). Thebreast volume contained a concentration of about 0.08 μCi/ml and thelesion concentration was about 6:1 over that of the breast. Imaging wasconducted for about 20 minutes and image reconstruction was completedusing a classical back-projection tomography techniques.

FIG. 9A shows phantom images from the single gamma camera system, withthe resulting images from the Tc⁹⁹ single gamma case. The planar imagesfrom the two detector positions and the resulting image from both fusiontechniques were shown in unsmoothed (see Panel I) and smoothed sets (seePanel II). The Contrast Map images (see Panel III) and the GeometricMean images (see Panel IV) are also shown. About a 3×3 mean smoothingkernel was used for image processing.

Vertical lineouts through the center of the lesion are shown in FIG. 9B.In order to facilitate direct comparison, the lineout data for each ofthe detectors, as shown in Panel I, was normalized such that the averagebackground is equal to about 100. The contrast map technique and thegeometric mean technique are both illustrated in Panel II, where thecontrast map technique provided the best contrast in this comparison.The noise level for both of the processed images was calculated bypropagating the noise level from each detector images (square root ofthe mean pixel value) through the image processing algorithm. The lesioncontrast and S:N for each image is listed in Table 2, immediately below.

TABLE 2 Detector 1 Detector 2 Contrast Map Geometric Mean Contrast 0.140.26 0.45 0.20 S:N 3.1 5.6 3.5 2.5

The contrast map technique demonstrated a better S:N ratio than thegeometric mean image, but poorer than that of the image from detector 2.Given the poor performance of the geometric mean method, it was notcalculated for the second experiment presented in Example 2, infra.

FIG. 10A shows 10 minute static acquisitions from different detectorhead positions and the contrast map image in an example using principlesof the invention. The resulting images from the PEM system. Thereconstruction plane was at the center of the lesion and was displayedas unsmoothed in Panel I and smoothed in Panel II. The phantombackground was prepared to simulate an average expected FDG breasttissue uptake level of about 0.092 mCi/cc. An acceptance angle of about20° was used for the image reconstruction.

FIG. 11A shows an unsmoothed (Panel I) and smoothed (Panel II) imagesfrom PEM system using a phantom filled with F-18 (6:1 lesion-to-phantomconcentration ration). FIG. 11B shows a vertical lineout through thelesion from the unsmoothed PEM image from FIG. 11A. this lineout throughthe center of the lesion clearly demonstrating the lesion signal. Table3, shown immediately below, provides the contrast and S:N ratio for theresulting PEM image. The contrast measured for the contrast maptechnique (Table 2) is slightly better than that of the PEM system(Table 3), but the higher sensitivity of the PEM system provided higherimaging statistics and therefore an improved S:N.

TABLE 3 PEM Image Contrast 0.37 S:N 4.98

Specific Example 2

In the second experiment, about a 4.5 cm thick compressed breast phantomwith a Tc99m concentration of 0.9 μCi/ml was prepared containing threelesions (two of about 8 mm diameter and one of about 6 mm diameter)containing an about 6:1 concentration over background and two 10 minutestatic acquisitions were obtained. A SPECT acquisition was performedwith the same lesions and background solution transferred to acylindrical (“uncompressed”) phantom with a diameter of about 9.25 cm.The SPECT acquisition angular sampling was set at about 3 degrees/stepand the imaging time was set at about 30 seconds/frame. These parameterswere selected to simulate about a 40 minute patient imaging time with adual head system. Image reconstruction was obtained using a filteredback-projection technique.

In the planar imaging case, both the about 8 mm lesions and the about 6mm lesion were visible in detector position 1 (Panel I of FIG. 10A).However, the about 6 mm lesion was not seen from detector position 2(Panel II of FIG. 10A). These results demonstrated that the impact ofcollimator to lesion distance on lesion signal as the lesion was locatedabout 1 cm from the collimator in the detector position 1 and about 4 cmfrom the detector position 2. In addition, the about 6 mm lesion signalwas clearly enhanced in the contrast map image of Panel III in FIG. 10A.

Vertical lineouts through each of the three lesions are shown in PanelsI, II and II of FIG. 10B. Each normalized graph displayed the lineoutsfrom the planar images and the processed image. In FIG. 10B, Panel Icorresponds to Panel I of FIG. 10A, Panel II corresponds to Panel II ofFIG. 10A, and Panel III corresponds to Panel III of FIG. 10A. Thecontrast for all lesions was enhanced in the contrast map image. Inaddition, S:N and contrast ratios were calculated for the contrast mapimage and are shown in Table 3 for reference.

In the second portion of this experiment, the cylindrical phantom wasloaded with the background solution and lesions used in the planarstudy. The SPECT images (plane thickness of about 0.5 cm) of thecylindrical phantom demonstrated visibility for the about 8 mm lesions,but failed to visualize the about 6 mm lesion although it was locatedonly about 1 cm from the cylinder wall, as shown in FIG. 12A. Inaddition, the center mounting rod was seen in Panels III and IV as avertical cold line through the center of the phantom. The lineout graphsin FIG. 12B are vertical profiles through the center of the about 8 mmlesions. In FIG. 12B, Panel I corresponds to Panel II in FIG. 12A andPanel II corresponds to Panel VII in FIG. 12A. Note that in Table 4,below, the SPECT S:N and contrast were comparable to that of the planarcase (Table 3) for the about 8 mm lesions, but that the about 6 mmlesion is not seen in the SPECT images.

TABLE 4 Frame 2 Frame 7 (8 mm) (8 mm) 6 mm lesion Contrast 0.48 0.55 N/AS:N 4.80 5.50 N/A

As the lesion signal versus the lesion depth in “tissue” relationshipbecame a more apparent limitation, a dual head detector concept wasdeveloped. The dual head system may be very useful in clinicalsituations where lesion location is not known a priori. This exampledemonstrated that two opposing about 5 minute to about 10 minute staticviews of the compressed breast combined by the geometric mean methodproduce a final image contrast comparable to that obtained fromtomographic techniques. In addition, this method was significantlyeasier to clinically implement and required less imaging time thantomographic imaging. The opposed views may be obtained using a dual-headsystem or by repositioning a single detector head. In the latter case,an independent compression paddle system may enable stable breastimaging geometry while repositioning the detector head.

Specific Example 3

The patients enlisted in this study (N=55) were selected after asuspicious finding was reported in a routine X-ray screening mammogram.Using the mammographic films as guidance, the patients were placed onthe stereotactic system table and the breast was compressed with a 5cm×5 cm compression paddle (mean compression tissue thickness of about5.96 cm, SD= about 1.41 cm). Scout views were obtained with the X-raysystem until it was verified that the region-of-concern demonstrated inthe mammogram was in the field-of-view. The mini gamma camera was thenmounted to the X-ray system gantry in the needle driver position, seeFIG. 1. A radiotracer was administered via venous puncture and anacquisition was initiated at the time of injection for about 10 minutes.Digital X-ray images were stored as high-resolution tiff images, andabout 10-minute static gamma camera images were obtained for allpatients. Additionally, dynamic data was stored in list mode for 33 ofthe 55 cases and radiotracer time uptake curves were generated for eachof these cases. Each of the patients returned the following day forneedle biopsy and these results are shown in Table 5, infra (theasterisked items indicate carcinoma).

TABLE 5 Lesion Type Number *Ductal carcinoma-well differentiated 6*Ductal carcinoma-moderately differentiated 3 * Mucinous carcinoma 1 *Ductal carcinoma in situ 3 Fibrocystic change 22 Fibrocystic change withmicrocalcifications 12 Fat necrosis 1 Sclerosing adenosis withmicrocalcifications 2 Atypical hyperplasia 2 Fibroadenoma 3

In standard stereotactic needle biopsy procedures, X-ray densities suchas dense masses, scar tissue and/or calcifications may be used todetermine the optimal area for tissue biopsy; therefore, densities mayindicate disease and their location may be spatially correlated toregions of diseased tissue.

A clinical study was conducted where each patient image set included adigital X-ray, a gamma image, and an overlay image for comparison (FIG.13). Of the 55 studies completed, 25 demonstrated non-uniformradiotracer uptake allowing spatial comparison with the X-ray. Of thesecases there were 13 cancers with focal uptake, 10 negative studies withlow patchy uptake, and 1 false negative (mucinous carcinoma) with aphotopenic region. Each image set was given a spatial registrationagreement grade from I to III. Grade I representing high spatialcorrelation, Grade II good spatial correlation (less than about ±5 mmdifferential) and Grade III, poor correlation (greater than about ±5 mmdifferential). There were 18 Grade I, 5 Grade II and 2 Grade III cases.One of the Grade II studies was a ductal carcinoma case which presentedas microcalcifications without defined mass in the X-ray image and focalradiotracer uptake in the gamma image. This focal uptake, however, wasnot superimposed with the calcifications (FIG. 14). In cases such asthis, the scintimammography image may provide better localization forneedle biopsy targeting. Both Grade III cases consisted of poorlycorrelated mild patchy uptake.

Dynamic radiotracer uptake acquisitions are in wide use for severalother nuclear medicine studies, but have not been investigated in thisapplication due to the limitations of clinical instrumentation. The SFOVgamma camera designed for this system excluded extramammary radiotraceruptake from the acquisition and enabled a dynamic study of the tracerdistribution in the breast tissue. List mode acquisitions for 33patients were used to reconstruct time uptake curves with about a 30second integration time per data point (FIG. 15). In FIG. 15, each graphcontained a baseline tissue uptake curve (BKG) and an area-of-concern(AOC) uptake curve for about a 4 pixel (about 6.6 mm× about 6.6 mm)region. The AOC was drawn on the area of focal uptake for positive gammaimages. For negative radiotracer studies, a region was spatiallycorrelated with the location of radiodensity in the X-ray image. Ofthese 33 cases, 9 were infiltrating carcinoma, 2 were ductal carcinomain situ, 1 was a fibroadenoma, and the remaining 21 were negativestudies.

Evaluation of the dynamic data yielded several interesting observations.First, nearly all cases demonstrated an oscillation of counts in therange of about 30 second to about 60 second cycles for both the AOC andBKG regions. This oscillation was significantly greater than could beexpected from statistical noise and may indicate some blood flow ortransient redistribution effects. In addition, initial radiotraceruptake was rapidly occurring within the first 2 minutes, and it wasdetermined that it is possible to obtain useful diagnostic images withthis SFOV detector using about a 3 minute acquisition time. Thisacquisition time is significantly less than the about 10 minutescurrently necessary for clinical scintimammographic and would allowgreater compression to be used that in turn improves lesion contrast andtherefore study sensitivity. Lastly and perhaps most significantly, thetime uptake curves obtained in this study add to the diagnostic value ofscintimammography by potentially distinguishing between false positiveand true positive studies.

Several methods of evaluating the dynamic study data were tested. First,the rise time of the AOC to determine if there was a relationshipbetween the slope of the uptake curve and lesion histology wasevaluated, subsequently no correlation was found. In addition, contrastand signal-to-noise ratios were plotted as a function of time; norelationship between these values and tumor type was observed. Sinceboth contrast and signal-to-noise ratios are based on subtracting thelesion signal from the background signal, it was hypothesized thatcalculations may not be sensitive enough to indicate minute trends intracer uptake and washout. By plotting the ratio of the lesion ROI overthe background ROI as a function of time and applying a linear fit tothe data points of each case, it was observed that all true positiveshad an increasing linear trend and that all false positives had anegative linear trend (FIG. 16).

The data processing and analysis methods developed for this studypositively impact the clinical value of scintimammographic studies. Theresults provided in this example may indicate that lesion malignancy canbe determined with a high degree of accuracy without biopsy, see Table2, infra.

TABLE 6 True positive 10 True negative 42 False positive 1 (1-epithelialhyperplasia) no uptake curve available False negative 1 (mucinous Ca)very low grade lesion Sensitivity 90.9% Specificity 97.7% PPV 90.9% NPV97.7% Accuracy 94.5%

Table 6 shows the results of 55 cases (only 33 of which contain uptakecurves) showing the high negative predictive value. In sum, the lessinvasive nature of these studies spares the patient of physical andemotional trauma and would significantly reduce the cost of managingcases of suspicious mammographic studies.

The examples given above are merely illustrative and are not meant to bean exhaustive list of all possible embodiments, applications ormodifications of the invention. Thus, various modifications andvariations of the described methods and systems of the invention will beapparent to those skilled in the art without departing from the scopeand spirit of the invention. Although the invention has been describedin connection with specific embodiments, it should be understood thatthe invention as claimed should not be unduly limited to such specificembodiments. Indeed, various modifications of the described modes forcarrying out the invention which are obvious to those skilled in thecellular and molecular biology fields or related fields are intended tobe within the scope of the appended claims.

The disclosures of all references and publications cited above areexpressly incorporated by reference in their entireties to the sameextent as if each were incorporated by reference individually.

1. A method for controlling a device for determining a lesion locationwithin a target site in a patient, the steps comprising: controllingmovement of at least one photon imaging device, wherein said at leastone photon imaging device is movable with respect to the target sitesuch that the at least one photon imaging device acquires a plurality ofimages relative to the target site, where a signal intensity and theplurality of images is obtained from opposed positions; receiving imagesfrom said at least one photon imaging device and receiving the signalintensity for each of the plurality of images; and calculating thelesion location within the target site in the patient based upon theplurality of images acquired by said at least one imaging device usingthe obtained signal intensities from only a single set of mutuallyopposing positions.
 2. The method of claim 1, further comprisingproviding at least one gantry for mounting the at least one photonimaging device.
 3. The method of claim 2, wherein the at least onephoton imaging device is a plurality of photon imaging devices.
 4. Themethod of claim 3, wherein the plurality of photon imaging devicesincludes a first photon imaging device comprising an x-ray generatormounted on the at least one gantry, a second photon imaging devicecomprising an x-ray detector mounted on the at least one gantry, and athird photon imaging device comprising a gamma camera mounted on the atleast one gantry.
 5. The method of claim 4, further comprising providinga fourth imaging device comprising a gamma camera mounted on the atleast one gantry.
 6. The method of claim 4, wherein the at least onegantry is a plurality of gantries and the first photon imaging deviceand the third photon imaging device are each mounted on separategantries, wherein the separate gantries are movable with respect to eachanother.
 7. The method of claim 2, wherein the at last one gantry is aplurality of gantries and a first photon imaging device is a gammacamera mounted on a first gantry of the plurality of gantries, a secondimaging device is an x-ray generator mounted on a second gantry of theplurality of gantries, and a third imaging device is an x-ray detectormounted on the second gantry.
 8. The method of claim 7, furthercomprising providing a fourth photon imaging device comprising a gammacamera mounted on said first gantry.
 9. The method of claim 7, whereinthe first gantry and the second gantry comprise concentric ringsmoveable with respect to each other.
 10. The method of claim 1, whereinin the step of controlling movement of the at least one photon imagingdevice to image the target site, the target site includes one or moresites selected from the group consisting of: breast, thyroid,parathyroid, heart, liver, kidney, gall bladder, bladder, reproductiveorgans and glandular structures.
 11. The method of claim 1, wherein thesignal intensity includes a comparative signal intensity calculated fromat least one of: comparing changes in attenuation, comparing changes inspatial resolution and comparing changes in partial volume effect. 12.The method of claim 1, wherein the signal intensity includes acomparative signal intensity calculated from at least two of: comparingchanges in attenuation, comparing changes in spatial resolution andcomparing changes in partial volume effect.